1. Field of the Invention
The present invention is directed to a doxycycline metal complex. More particularly, the present invention is directed to a solid dosage form of a doxycycline metal complex.
2. Related Background Art
Doxycycline (6-deoxy-5-hydroxytetracycline monohydrate) is a broad spectrum bacteriostatic compound that is effective against gram-positive, gram-negative, aerobic and anaerobic bacteria, as well as spirochetes, mycoplasmas, rickettsiae, chlamydiae and some protozoans. It works by inhibiting protein synthesis in bacteria or protozoans, which effectively kills them. It is commonly used in the treatment of bacterial infections caused by these organisms, such as urinary tract infections, upper respiratory tract infections, acne, gonorrhea, chlamydia, anthrax, lyme disease and others.
Individuals taking doxycycline, are advised that iron supplements, multivitamins, calcium supplements, antacids, or laxatives should be avoided. These products can adversely reduce the efficacy of doxycycline by reducing its absorption in the body.
British Patent No. 1,360,998 to Villax describes a process for isolation of α-6-deoxytetracyclines from a crude reaction mixture. The patent also discloses that calcium salts of tetracyclines are suitable for oral preparations such as suspensions. However, calcium salts of doxycycline are known to be particularly unstable in an alkaline pH environment. Moreover, the process described by Villax, uses an organic solvent, i.e., methanol. While organic solvents are often used to prepare pharmaceutically active ingredients, they are generally not desirable in the process of preparing a solid dosage form containing a pharmaceutically active ingredient. Clearly, the process disclosed in Villax for isolating the deoxytetracyclines would not result in a solid dosage form suitable for pharmaceutical administration to humans due to residual solvent.
Doxycycline is a very bitter tasting drug. Currently, a doxycycline metal salt is only available as a suspension of doxycycline calcium. An advantage of the doxycycline calcium complex suspension is that it has an acceptable taste. But many individual's find a liquid dosage form inconvenient. Having no real alternative, i.e., a solid dosage form of a doxycycline metal complex, they must put up with the inconvenience.
Another source of doxycycline is doxycycline hyclate. However, it can cause complications, such as esophageal ulceration. This would not be a problem with a solid dosage form of doxycycline. For example, a doxycycline calcium complex chewable tablet, if available, would not cause ulceration of the esophagus because the drug would not be soluble and therefore would pass through the esophageal environment without harming it.
However, making a solid dosage form of a doxycycline metal complex is extremely difficult. For example, it is not known how to filter a doxycycline metal complex in an aqueous suspension, such as doxycycline calcium complex. Prior art methods have not made it possible to obtain reasonably pure doxycycline metal complex from an aqueous solution.